The development of an organism depends on the expression of individual genes and the integration of the products of those genes into units of function. Considerable progress is being made in understanding regulation of gene expression and the direction of future research in that area is becoming apparent. However, virtually nothing is known about the integration into functional units of the products of genes which are essential for various developmental processes. The overall goal of the research in this laboratory is to use the imaginal discs of Drosophila as a model system to discover principles according to which such gene products are integrated into units of function. The potential significance of discovering such principles is that it could facilitate understanding such abnormal human developmental processes as congenital abnormalities and cancer, it could provide insights into increasing the regeneration potential of damaged organs, and it could stimulate new research approaches to the aging process. Many genes which are essential for imaginal disc development in Drosophila have been identified by mutations which cause imaginal disc abnormalities. The analysis of such mutations has led to significant generalizations about imaginal disc development. However, the analysis of such mutations has not, in general, provided useful clues as to the identity of the normal products of those genes nor to their biochemical function. The long-term objective of the proposed research is to identify the primary products of the genes identified by such mutations in order to begin analyzing their biochemical function in imaginal disc development. The specific aims of this proposal are to use two different approaches to isolate those sequences of DNA which correspond to genes identified by mutations. One approach will utilize DNA-mediated transformation of tissue culture cells derived from temperature-sensitive mutants. The other approach will utilize hybrid dysgenesis to induce insertion mutations. Once such DNA sequences are isolated by either method, they will be used as probes to examine the pattern of transcription of the corresponding genes. Those transcripts which are detected will be tested for their ability to be translated in vitro to identify the polypeptides for which they code. The identification of protein products of such genes will be an important step towards understanding the function of those genes, especially when combined with information already obtained about the phenotype caused by mutations in those genes.